The α1-adrenoceptor-mediated human hyperplastic prostate cells proliferation is impaired by EGF receptor inhibition

Benign prostatic hyperplasia (BPH) is an aging-related and progressive disease linked to an up-regulation of alpha(1)-adrenoceptors. The participation of EGF receptors (EGFR) in the GPCRs' signalosome has been described but so far data about the contribution of these receptors to prostatic stromal hyperplasia are scanty. We isolated and cultured vimentin-positive prostate stromal cells obtained from BPH patients. According to intracellular Ca2+ measurements, cell proliferation and Western blotting assays, these cultured hyperplastic stromal cells express functional alpha(1)-adrenoceptors and EGFR, and proliferate in response to the alpha(1)-adrenoceptor agonist phenylephrine. Interestingly, in these cells the inhibition of EGFR signaling with GM6001, CRM197, AG1478 or PD98059 was associated with full blockage of alpha(1)-adrenoceptor-mediated cell proliferation, while cell treatment with each inhibitor alone did not alter basal cell growth. Moreover, the co-incubation of AG1478 (EGFR inhibitor) with a alpha(1A)/alpha(1D)-adrenoceptor antagonists showed no additive inhibitory effect. These findings highlight a putative role of EGFR signaling to alpha(1)-adrenoceptor-mediated human prostate hyperplasia, suggesting that the inhibition of this transactivation cascade could be useful to reduce BPH progression.